New effects of caffeine on CRH-induced stress along the intrafollicular classical HPA-axis (CRH-R1/2, IP3 -R, ACTH, MC-R2) and the neurogenic non-HPA-axis (substance P, p75NTR and TrkA) in ex vivo human male androgenetic scalp hair follicles.

Br J Dermatol. 2020 Apr 9. doi: 10.1111/bjd.19115. [Epub ahead of print]
New effects of caffeine on CRH-induced stress along the intrafollicular classical HPA-axis (CRH-R1/2, IP3 -R, ACTH, MC-R2) and the neurogenic non-HPA-axis (substance P, p75NTR and TrkA) in ex vivo human male androgenetic scalp hair follicles.
Fischer TW1,2, Bergmann A1, Kruse N1, Kleszczynski K1, Skobowiat C3, Slominski AT3,4,5, Paus R1,6,7,8.

Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuro-endocrine equivalent of the systemic hypothalamic-pituitary-adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used the HPA axis triggering corticotropin-releasing hormone (CRH) to induce a stress response in human ex vivo male AGA HFs. Furthermore, since caffeine is known to reverse testosterone-mediated hair growth inhibition in the same hair organ culture model, we investigated whether caffeine would antagonize CRH-mediated stress in these HFs. HFs from balding vertex area scalp biopsies of AGA-affected men were incubated with CRH (10-7 M) and with/without caffeine (0.001%, 0.005%). Compared to controls, CRH significantly enhanced the expression of catagen-inducing TGF-β2 (p<0.001), CRH receptors 1/2 (p<0.01), ACTH (p<0.001) and melanocortin-receptor-2 (MC-R2) (p<0.001), and additional stress-associated parameters, substance P and p75 neurotrophin receptor. CRH inhibited matrix keratinocyte proliferation and expression of anagen-promoting IGF-1 and pro-proliferative nerve growth factor receptor TrkA. Caffeine significantly counteracted all described stress effects and additionally enhanced IP3 -R, first time detected in human HFs. These findings provide the first evidence in ex vivo human AGA HFs, that the stress mediator CRH induces not only a complex intrafollicular HPA, but also a non-HPA related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss, and that caffeine may effectively counteract stress-induced hair damage and possibly prevent stress-induced hair loss.

KEYWORDS:
ACTH; CRH; IGF-1 - IP3-R; MC-R2; TGFβ2; TrkA; androgenetic alopecia; caffeine; human hair follicles; hypothalamic-pituitary-adrenal axis; p75NTR; substance P

Isn't this contradictory evidence to what was previously known ?

Nuada wrote:Isn't this contradictory evidence to what was previously known ?

The distinction here is topical verses internal.  That makes all the difference in the world.

This is my observation as well. Topical caffeine yes, internal yes if you are willing to pay for taxes. In my case tax is too high.

CausticSymmetry wrote:

Nuada wrote:Isn't this contradictory evidence to what was previously known ?

The distinction here is topical verses internal.  That makes all the difference in the world.

Oh I see. Didn't realize this was about topical caffeine.
Is there a specific way to apply caffeine topically ?

Yes, you can mix a drop of alcohol or DMSO to increase the absorption... The same kind of liquid - coffee would work... i like brewing it for my hair wash purposes.

I mix some magnesium sulphate to it, so the scalp is relaxed. I think topicals can really be used for rescue until internal hair loss factors are being tackled.
Another one is transdermal copper.

Best natural caffeine topical? Matcha Green tea or organic coffee? Something else?

@CS Would say a spoonful of coffee added to a handful of shampoo be effective say while washing in the shower every morning or should we maybe applying a caffeine oil and leaving it in all day?

Any way of preventing coffee topical from going bad ?

Auriga wrote:@CS Would say a spoonful of coffee added to a handful of shampoo be effective say while washing in the shower every morning or should we maybe applying a caffeine oil and leaving it in all day?

The whole trick is knowing exactly the right amount of caffeine. It's been over 15 years since I tried this, and I didn't bother with it long.

The reason was, if the amount wasn't perfect, or if you skipped a day, there would be a headache. 

There are caffeine shampoos available, at least there was.